US8785390B2ActiveUtilityA1

Methods for treatment of Alzheimer's disease

83
Assignee: JOHANSSON JANPriority: Jan 30, 2009Filed: Jan 29, 2010Granted: Jul 22, 2014
Est. expiryJan 30, 2029(~2.6 yrs left)· nominal 20-yr term from priority
Inventors:Jan Johansson
C07K 14/785A61P 25/28A61K 38/1709A61K 38/00A61K 38/395
83
PatentIndex Score
4
Cited by
67
References
17
Claims

Abstract

An isolated protein selected from the group consisting of (i) proteins comprising an amino acid sequence having at least 70% identity to the C-terminal domain of lung surfactant protein C precursor (CTproSP-C, “CTC”) from a mammal; and (ii) proteins comprising an amino acid sequence having at least 70% identity to the Brichos domain of CTproSP-C from a mammal, is disclosed for treatment of Alzheimer's disease in a mammal, including man.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A method of therapeutically treating or delaying progression of Alzheimer's disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an isolated protein, wherein the isolated protein delays or reduces amyloid fibril formation and aggregation of amyloid β peptide, and wherein the isolated protein is selected from:
 (a) a protein comprising an amino acid sequence having all conserved residues of mammalian C-terminal domain of lung surfactant protein C precursor (CTproSP-C) (SEQ ID NO: 11) and having at least 70% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or 
 (b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17). 
 
     
     
       2. The method of  claim 1 , wherein the subject is human. 
     
     
       3. The method of  claim 1 , wherein the isolated protein is selected from:
 (a) a protein comprising an amino acid sequence having all conserved residues of mammalian C-terminal domain of lung surfactant protein C precursor (CTproSP-C) (SEQ ID NO: 11) and having at least 70% identity to human CTproSP-C (SEQ ID NO: 2); or 
 (b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity to the Brichos domain of human CTproSP-C (SEQ ID NO: 4). 
 
     
     
       4. The method of  claim 1 , wherein the isolated protein has less than or equal to 200 amino acid residues. 
     
     
       5. The method of  claim 4 , wherein the isolated protein has less than or equal to 150 amino acid residues. 
     
     
       6. The method of  claim 1 , wherein the isolated protein has more than or equal to 90 amino acid residues. 
     
     
       7. The method of  claim 6 , wherein the isolated protein has more than or equal to 100 amino acid residues. 
     
     
       8. The method of  claim 1 , wherein the isolated protein is selected from the group consisting of:
 (a) CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); 
 (b) the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17); and 
 (c) an extended Brichos domain of human CTproSP-C having the amino acid sequence of SEQ ID NO: 21. 
 
     
     
       9. The method of  claim 8 , wherein the isolated protein is selected from the group consisting of human CTproSP-C (SEQ ID NO: 2), the Brichos domain of human CTproSP-C (SEQ ID NO: 4), and the extended Brichos domain of human CTproSP-C having SEQ ID NO: 21. 
     
     
       10. The method of  claim 1 , wherein a position corresponding to leucine-188 in human proSP-C (SEQ ID NO: 1) is not glutamine. 
     
     
       11. The method of  claim 10 , wherein the position corresponding to leucine-188 in human proSP-C (SEQ ID NO: 1) is strictly conserved. 
     
     
       12. The method of  claim 1 , wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 70% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
       13. The method of  claim 1 , wherein the isolated protein is selected from:
 (a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 80% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or 
 (b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 80% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17). 
 
     
     
       14. The method of  claim 13 , wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 80% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
       15. The method of  claim 13 , wherein the isolated protein is selected from:
 (a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 90% identity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or 
 (b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 90% identity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17). 
 
     
     
       16. The method of  claim 15 , wherein the isolated protein comprises an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 4, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
       17. The method of  claim 1 , wherein the isolated protein is selected from:
 (a) a protein comprising an amino acid sequence having all conserved residues of mammalian CTproSP-C (SEQ ID NO: 11) and having at least 70% identity and at least 90% similarity to the CTproSP-C from human (SEQ ID NO: 2), bovine (SEQ ID NO: 5), rhesus (SEQ ID NO: 6), mouse (SEQ ID NO: 7), mink (SEQ ID NO: 8), rabbit (SEQ ID NO: 9) or rat (SEQ ID NO: 10); or 
 (b) a protein comprising an amino acid sequence having all conserved residues of the Brichos domain of mammalian CTproSP-C (SEQ ID NO: 18) and having at least 70% identity and at least 90% similarity to the Brichos domain of CTproSP-C from human (SEQ ID NO: 4), bovine (SEQ ID NO: 12), rhesus (SEQ ID NO: 13), mouse (SEQ ID NO: 14), mink (SEQ ID NO: 15), rabbit (SEQ ID NO: 16) or rat (SEQ ID NO: 17).

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